The CDC said H3N2v viruses will be
positive for the nucleoprotein (NP) gene (pdmInfA), influenza A, and
seasonal influenza A (H3) targets of the CDC's rRT-PCR diagnostic
panel. All suspected novel influenza A and H3N2v samples should be sent
to the CDC for confirmational testing, it said. "Confirmation of influenza A (H3N2)v virus
is performed only at CDC at this time."

The agency urged health
departments to conduct contact tracing of confirmed, probable, or
suspected H3N2v cases and provided definitions for the three levels of
cases in a separate document. It asked health departments to notify the
CDC about all suspected and probable H3N2v infections within 24 hours
of identification.

The CDC defined a suspected
H3N2v case as an acute respiratory illness in a patient who has an
epidemiologic link to a confirmed case or got sick within 7 days of
swine exposure.

It said a probable case is
in a patient whose respiratory sample tested positive on the CDC RT-PCR
flu panel for influenza A, pandemic influenza A, and H3, but negative
for influenza B, pandemic H1, and H1. Also, a probable case could be in
a person who has an acute respiratory infection and a link to a
confirmed H3N2v case and whose diagnostic test is positive for
influenza A (H3) or influenza A (no subtype tested or detected).

The focus on H3N2v cases is linked to the two recent clusters in Iowa
and West Virginia. Both clusters were large and had no swine
linkage, as was seen in the initial H1N1pdm11 cases in 2009 in Southern
California. However, the H3N2v cases are more compelling because
the number of confirmed cases in each cluster is larger, and the five
confirmed cases in Iowa and West Virginia follow confirmed cases in
Indiana, Pennsylvania, and Maine which represent independent
introductions, yet have the same constellation and lineage for all 8
gene segments, which has not been found in any reported swine isolate
collected prior to the July and August human cases in Indiana and
Pennsylvania, and only one
public sequence, A/swine/NY/A01104005/2011.

However, as seen in the two clusters above, the number of cases is
markedly higher than the 12 confirmed cases in 2011 because many cases
were collected in the off season or early in the current season when
RNA levels in samples are low, and PCR test interpretation is highly
nuanced. Most of the H3N2v cases were identified because a
perceived swine exposure or linkage to a confirmed case led to CDC
testing of samples that initially tested as negative,
inconclusive,
unsubtypable, or seasonal H3, including testing with the newly
approved CDC PCR test.

Thus, it is likely that only a subset of H3N2v cases will be
identified, but the early release MMWR, coupled with the associated
documents, and last week’s 50 state conference call, will likely lead
to a bottleneck in testing, as was seen in 2009 when all confirmations
required CDC testing, which is the current situation for all novel
cases other than H1N1pdm09.

Moreover, recent results raise concerns that novel
human cases extend well beyond the 12 H3N2v cases reported in
2011. The recently reported H1N2v case in Minnesota (A/Minnesota/19/2011)
was also not linked to swine exposure, but was linked to an untested
symptomatic case. However, the Minnesota case was confirmed with
an isolate tested during routine screening, leading to a delay and
limited follow-up of contacts, including the symptomatic case.
Thus, the delectability of H1N2v cases in clinical samples remains
unclear. Similarly, the H1N1v
sample was positive for both H1N1pdm09 targets, but the signal for
H1 was markedly lower than NP, and the case had an occupational swine
exposure, leading to CDC testing. Other samples without a swine
exposure may be classified as H1N1pdm09 instead of H1N1v.

Thus, the requirement of confirmation by the CDC may lead to
significant confirmation delays, and limited confirmation of H1N1v and
H1N2v cases, which may significant increase as conditions for the
spread on influenza in the United States improve in January.

Thus, an explosion
of novel cases is expected in early 2012, but the true extent of
the genetic instability in human novel cases by be significantly
under-represented due to testing limitations.